Disease Chromosome Gene Product Inheritance Mutation

SCA1 6p23 ataxin-1 AD CAG in coding region

SCA2 12q24.1 ataxin-2 AD CAG in coding region

SCA3 14q21 ataxin-3 AD CAG in coding region

SCA4 16q22.1 ? AD ?

SCA5 11 ? AD ?

SCA6 19p13.1-2 a1A voltage-dependent calcium channel

subunit

AD CAG in coding region

SCA7 3p21.1-p12 ataxin7 AD CAG in coding region

SCA8 13q21 ? AD Untranslated

CTG repeat on antisense strand

SCA10 22q13 ataxin-10 AD Intronic

ATTTC repeat

SCA11 15q14-21 ? AD

SCA12 5q31 protein AD CAG in 5' UTR region

phosphatase 2A

SCA13 19q13 ? AD ?

SCA14 19q13.4 ? AD ?

SCA15 3pter-24.2 ? AD ?

SCA16 8q22.24 ? AD ?

SCA17 6q27 TATA-binding protein AD CAG in coding region

FA 9q13-21 frataxin-1 AR Intronic GAA repeat

Ataxia-telangiectasia 11q22-23 ATM AR Point mutations

Friedreich Ataxia

This is an autosomal-recessive progressive illness, generally beginning in the first decade of life with gait ataxia, followed by hand clumsiness and dysarthria. Deep tendon reflexes are

depressed or absent, but an extensor plantar reflex is typically present. Joint position and vibratory sense are impaired, and there is sometimes loss of pain and temperature sensation and

light touch. Most patients develop pes cavus and kyphoscoliosis. There is a high incidence of cardiac disease with arrhythmias and congestive heart failure. Concomitant diabetes is

found in about 10% of patients. Most patients become wheelchair-bound within about 5 years of onset; the cause of death is intercurrent pulmonary infections and cardiac disease.

The gene for Friedreich ataxia has been mapped to chromosome 9q13, and in most cases, there is a GAA trinucleotide repeat expansion in the first intron of a gene encoding a protein

named frataxin.[218] Affected individuals inherit abnormal forms of the frataxin gene from both parents and have extremely low levels of the protein. In some cases of Friedreich ataxia,

one of the mutant alleles harbors a missense or nonsense mutation. Frataxin undergoes processing and ends up in the inner mitochondrial membrane, where it has been suggested to play

a role in regulation of iron levels.[219] [220] Because of the need for this metal in many of the complexes of the oxidative phosphorylation chain, mutations in frataxin have been

suggested to result in generalized mitochondrial dysfunction. Thus, Friedreich ataxia shares biologic features with other spinocerebellar ataxias (anatomic distribution of pathology,

trinucleotide repeat expansion) and the mitochondrial encephalopathies.

Morphology.

The spinal cord shows loss of axons and gliosis in the posterior columns, the distal portions of corticospinal tracts, and the spinocerebellar tracts. There is degeneration of neurons in the

spinal cord (Clarke column), the brainstem (cranial nerve nuclei VIII, X, and XII), the cerebellum (dentate nucleus and the Purkinje cells of the superior vermis), and to some extent the

Betz cells of the motor cortex. Large dorsal root ganglion neurons are also decreased in number; their large myelinated axons, traveling first in the dorsal roots and then in dorsal

columns, therefore undergo secondary degeneration. The heart is enlarged and may have pericardial adhesions. Multifocal destruction of myocardial fibers with inflammation and

fibrosis is detectable in about half the patients who come to autopsy examination.

Date: 2016-04-22; view: 819